ABSTRACT- CLINICAL CORE The Clinical Core (CC) is central to the function of the NYU ADRC by providing comprehensive evaluations and accurate research diagnoses for participants engaged in its long-standing longitudinal study of normal versus pathologic cognitive aging. The CC has made significant advances in the characterization of preclinical to dementia stages: establishing subjective cognitive decline as a prodromal stage, developing widely used scales for clinical phenotyping, and helping establish important imaging biomarkers of early stage disease. We continue our goal to understand mechanisms that influence transitions towards dementia. We emphasize the study of critical, early transitions (normal->preclinical/prodromal->MCI) and how they relate to state-of-the-art biomarkers of the ATN framework and AD/ADRD heterogeneity. Our approach will combine standard UDS 3 assessments with an innovative NYU-specific protocol that uses advanced MR and PET neuroimaging, robust clinical phenotyping schemes, and new biofluid/disease monitoring strategies. We propose 4 specific aims. Aim 1 is to comprehensively characterize a cohort of ~500 community-dwelling older adults [70% normal, 20-25% MCI, 40% from Black/African-American and Latino groups] with (a) a unique protocol for longitudinal clinical phenotyping and biomarker analysis to evaluate preclinical/prodromal disease and AD/ADRD heterogeneity, (b) timely data reporting to participants and national repositories, and, (c) brain donation consenting to establish clinical- biomarker-pathological correlations. Aim 2 is to support a large network of interventional AD/ADRD trials and in- house affiliated studies on multi-etiology dementia by maintaining a dynamic registry of ?study-ready? participants. Aim 3 is to improve the clinical phenotyping of at-risk/early stage subjects by (a) developing novel characterization schemes for neuropsychiatric symptoms and SCD and (b) leveraging emerging technology to investigate digital biomarkers related to cognition, sleep, and motor function. Aim 4 is to improve clinical skills of dementia practitioners, promote the use of CC data for AD/ADRD research among early career investigators, and educate the public about AD/ADRD and the value of normal controls and brain/biospecimen donation. These aims allow the CC to advance its state-of-the-art program that is well poised to answer critical questions within the current AD/ADRD research framework and contribute to NAPA research implementation milestones.